Inhalation of carbon monoxide following resuscitation ameliorates hemorrhagic shock-induced lung injury

Kawanishi,Susumu; Takahashi,Toru; Morimatsu,Hiroshi; Shimizu,Hiroko; Omori,Emiko; Sato,Kenji; Matsumi,Masaki; Maeda,Shigeru; Nakao,Atsunori; Morita,Kiyoshi

doi:10.3892/mmr.2012.1173

Inhalation of carbon monoxide following resuscitation ameliorates hemorrhagic shock-induced lung injury

Authors:
- Susumu Kawanishi
- Toru Takahashi
- Hiroshi Morimatsu
- Hiroko Shimizu
- Emiko Omori
- Kenji Sato
- Masaki Matsumi
- Shigeru Maeda
- Atsunori Nakao
- Kiyoshi Morita
View Affiliations

Affiliations: Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama 700‑8558, Japan, Department of Dental Anesthesiology, Okayama University Dental School, Okayama 700-8558, Japan, Department of Emergency and Critical Care Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Published online on: November 8, 2012 https://doi.org/10.3892/mmr.2012.1173
Pages: 3-10

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Even after successful resuscitation, hemorrhagic shock frequently causes pulmonary inflammation that induces acute lung injury (ALI). We previously demonstrated that when CO is inhaled at a low concentration both prior to and following hemorrhagic shock and resuscitation (HSR) it ameliorates HSR-induced ALI in rats due to its anti-inflammatory effects. In the present study, we administered CO to the same model of ALI only after resuscitation and examined whether it exerted a therapeutic effect without adverse events on HSR-induced ALI, since treatment of animals with CO prior to HSR did not prevent lung injury. HSR were induced by bleeding animals to achieve a mean arterial pressure of 30 mmHg for 1 h followed by resuscitation with the removed blood. HSR resulted in the upregulation of inflammatory gene expression and increased the rate of apoptotic cell death in the lungs. This was determined from an observed increase in the number of cells positive for transferase-mediated dUTP-fluorescein isothiocyanate (FITC), nick-end labeling staining and activated caspase-3. HSR also resulted in prominent histopathological damage, including congestion, edema, cellular infiltration and hemorrhage. By contrast, CO inhalation for 3 h following resuscitation significantly ameliorated these inflammatory events, demonstrated by reduced histological damage, inflammatory mediators and apoptotic cell death. The protective effects of CO against lung injury were notably associated with an increase in the protein expression level of peroxisome proliferator-activated receptor (PPAR)-γ, an anti-inflammatory transcriptional regulator in the lung. Moreover, CO inhalation did not affect the hemodynamic status or tissue oxygenation during HSR. These findings suggest that inhalation of CO at a low concentration exerts a potent therapeutic effect against HSR-induced ALI and attenuates the inflammatory cascade by increasing PPAR-γ protein expression.

View Figures

View References

1	Bhatia M and Moochhala S: Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol. 202:145–156. 2004. View Article : Google Scholar : PubMed/NCBI
2	Hudson LD, Milberg JA, Anardi D and Maunder RJ: Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 151:293–301. 1995. View Article : Google Scholar : PubMed/NCBI
3	Kollef MH and Schuster DP: The acute respiratory distress syndrome. N Eng J Med. 332:27–37. 1995. View Article : Google Scholar : PubMed/NCBI
4	Bernard GR, Artigas A, Brigham KL, et al: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 149:818–824. 1994. View Article : Google Scholar
5	Foresti R, Bani-Hani MG and Motterlini R: Use of carbon monoxide as a therapeutic agent: promises and challenges. Intensive Care Med. 34:649–658. 2008. View Article : Google Scholar : PubMed/NCBI
6	Otterbein LE, Mantell LL and Choi AM: Carbon monoxide provides protection against hyperoxic lung injury. Am J Physiol. 276:L688–L694. 1999.PubMed/NCBI
7	Sarady JK, Zuckerbraum BS, Bilban M, et al: Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J. 18:854–856. 2004.PubMed/NCBI
8	Zhang X, Shan P, Otterbein LE, et al: Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J Biol Chem. 278:1248–1258. 2003. View Article : Google Scholar
9	Zuckerbraun BS, McCloskey CA, Gallo D, Liu F, Ifedigbo E, Otterbein LE and Billiar TR: Carbon monoxide prevents multiple organ injury in a model of hemorrhagic shock and resuscitation. Shock. 23:527–532. 2005.PubMed/NCBI
10	Kanagawa F, Takahashi T, Inoue K, et al: Protective effect of carbon monoxide inhalation on lung injury following hemorrhagic shock/resuscitation in rats. J Trauma. 69:185–194. 2010. View Article : Google Scholar : PubMed/NCBI
11	Kikenny C, Browne WJ, Cuthill IC, Emerson M and Aitman DG: Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. J Pharmacol Pharmacother. 1:94–99. 2010. View Article : Google Scholar : PubMed/NCBI
12	Inoue K, Takahashi T, Uehara K, et al: Protective role of heme oxygenase 1 in the intestinal tissue injury in hemorrhagic shock in rats. Shock. 29:252–261. 2008. View Article : Google Scholar : PubMed/NCBI
13	Murakami K, McGuire R, Cox RA, et al: Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep. Shock. 18:236–241. 2002. View Article : Google Scholar : PubMed/NCBI
14	Zegdi R, Fabre O, Cambillau M, et al: Exhaled nitric oxide and acute lung injury in a rat model of extracorporeal circulation. Shock. 20:569–574. 2003. View Article : Google Scholar : PubMed/NCBI
15	Jiang H, Meng F, Li W, Tong L, Qiao H and Sun X: Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats. Surgery. 141:32–40. 2007. View Article : Google Scholar : PubMed/NCBI
16	Umeda K, Takahashi T, Inoue K, et al: Prevention of hemorrhagic shock-induced intestinal tissue injury by glutamine via heme oxygenase-1 induction. Shock. 31:40–49. 2009. View Article : Google Scholar : PubMed/NCBI
17	Maeshima K, Takahashi T, Uehara K, et al: Prevention of hemorrhagic shock-induced lung injury by heme arginate treatment in rats. Biochem Pharmacol. 69:1667–1680. 2005. View Article : Google Scholar : PubMed/NCBI
18	Sunil VR, Patel KJ, Nilsen-Hamilton M, Heck DE, Laskin JD and Laskin DL: Acute endotoxiemia is associated with upregulation of lipocalin 24p3/Lcn2 in lung and liver. Exp Mol Pathol. 83:177–187. 2007. View Article : Google Scholar : PubMed/NCBI
19	Faleo G, Neto JS, Kohmoto J, et al: Carbon monoxide ameliorates renal cold ischemia-reperfusion injury with an upregulation of vascular endothelial growth factor by activation of hypoxia-inducible factor. Transplantation. 85:1833–1840. 2008. View Article : Google Scholar
20	Ciesla DJ, Moore EE, Johnson JL, Burch JM, Cothren CC and Sauaia A: The role of the lung in postinjury multiple organ failure. Surgery. 138:749–757. 2005. View Article : Google Scholar : PubMed/NCBI
21	Kohmoto J, Nakao A, Stolz DB, et al: Carbon monoxide protects rat lung transplants from ischemia-reperfusion injury via a mechanism involving p38 MAPK pathway. Am J Transplant. 7:2279–2290. 2007. View Article : Google Scholar : PubMed/NCBI
22	Song R, Kubo M, Morse D, et al: Carbon monoxide induces cytoprotection in rat orthotopic lung transplantation via anti-inflammatory and anti-apoptotic effects. Am J Pathol. 163:231–242. 2003. View Article : Google Scholar : PubMed/NCBI
23	Zuckerbraun BS, Chin BY, Wegiel B, et al: Carbon monoxide reverses established pulmonary hypertension. J Exp Med. 203:2109–2119. 2006. View Article : Google Scholar : PubMed/NCBI
24	Nemzek JA, Fry C and Abatan O: Low-dose carbon monoxide treatment attenuates early pulmonary neutrophil recruitment following acid aspiration. Am J Physiol Lung Cell Mol Physiol. 294:L644–L653. 2008. View Article : Google Scholar : PubMed/NCBI
25	Goebel U, Siepe M, Schwer CI, et al: Postconditioning of the lungs with inhaled carbon monoxide following cardiopulmonary bypass in pigs. Anesth Analg. 112:282–291. 2011. View Article : Google Scholar : PubMed/NCBI
26	Otterbein LE, Bach FH, Alam J, et al: Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med. 6:422–428. 2006.PubMed/NCBI
27	Sarady JK, Otterbein SL, Liu F, Otterbein LE and Choi AM: Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages. Am J Respir Cell Mol Biol. 27:739–745. 2002. View Article : Google Scholar
28	Morse D, Pischke SE, Zhou Z, et al: Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem. 278:36993–36998. 2003. View Article : Google Scholar : PubMed/NCBI
29	Nakahira K, Kim HP, Geng XH, et al: Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts. J Exp Med. 203:2377–2389. 2006. View Article : Google Scholar : PubMed/NCBI
30	Bilban M, Bach FH, Otterbein SL, et al: Carbon monoxide orchestrates a protective response through PPARgamma. Immunity. 24:601–610. 2006. View Article : Google Scholar : PubMed/NCBI
31	Hoetzel A, Dolinary T, Vallbracht S, et al: Carbon monoxide protects against ventilator-induced via PPAR-gamma and inhibition of Egr-1. Am J Respir Crit Care Med. 177:1223–1232. 2008. View Article : Google Scholar : PubMed/NCBI
32	Abdelrahman M, Collin M and Thiemermann C: The peroxisome proliferator-activated receptor-gamma ligand 15-deoxyDelta 12,24 prostaglandin J2 reduces the organ injury in hemorrhagic shock. Shock. 22:555–561. 2004. View Article : Google Scholar : PubMed/NCBI
33	Chima RS, Hake PW, Piraino G, Mangeshkar P, Denenberg A and Zingarelli B: Ciglitazone ameliorates lung inflammation by modulating the increased inhibitor kappaB protein kinase/nuclear factor-kappaB pathway following hemorrhagic shock. Crit Care Med. 36:2849–2857. 2008. View Article : Google Scholar
34	Chima RS, Hake PW, Piraino G, Mangeshkar P, O'Connor M and Zingarelli B: Ciglitazone, a novel inhibitor of lung apoptosis following hemorrhagic shock. Int J Clin Exp Med. 3:1–9. 2010.PubMed/NCBI
35	Rodkey FL, O'Neal JD and Collison HA: Oxygen and carbon monoxide equilibria of human adult hemoglobin at atmospheric and elevated pressure. Blood. 33:57–65. 1969.PubMed/NCBI
36	Morse D, Sethi J and Choi AM: Carbon monoxide-dependent signaling. Crit Care Med. 30:S12–S17. 2001. View Article : Google Scholar : PubMed/NCBI
37	Mayr FB, Spiel A, Leitner J, et al: Effects of carbon monoxide inhalation during experimental endotoxemia in humans. Am J Respir Crit Care Med. 171:354–360. 2005. View Article : Google Scholar : PubMed/NCBI
38	Brittain T, Sutherland J and Greenwood C: A study of the kinetics of the reaction of ligands with the liganded states of mouse embryonic haemoglobins. Biochem J. 234:151–155. 1986.PubMed/NCBI
39	Wilson MR, O'Dea KP, Dorr AD, Yamamoto H, Goddard ME and Takata M: Efficacy and safety of inhaled carbon monoxide during pulmonary inflammation in mice. PLoS One. 5:e115652010. View Article : Google Scholar : PubMed/NCBI